P1013: OVERALL SURVIVAL IN PATIENTS WITH SYSTEMIC MASTOCYTOSIS WITH ASSOCIATED HEMATOLOGIC NEOPLASM TREATED WITH AVAPRITINIB VERSUS BEST AVAILABLE THERAPY
Authors: A. Reiter, J. Gotlib, I. Álvarez-Twose, D. H. Radia, J. Luebke, P. J. Bobbili, A. Wang, C. Norregaard, S. Dimitrijević, E. Sullivan, M. Louie-Gao, J. Schwaab, I. A. Galinsky, C. Perkins, W. R. Sperr, P. Sriskandarajah, A. Chin, S. R. Sendhil, M. S. Duh, P. Valent, D. J. DeAngelo
Journal: HemaSphere (2022)

Background: Avapritinib, a selective inhibitor of KIT D816V, was approved in the United States (US) for treatment of adults with advanced systemic mastocytosis (AdvSM), a rare myeloid neoplasm with poor overall survival (OS), based on data from the Phase 1 EXPLORER (NCT02561988) and Phase 2 PATHFINDER (NCT03580655) single-arm trials. Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) is both the most common and most heterogenous subtype of AdvSM. No randomized control trial (RCT) has been conducted comparing efficacy of avapritinib with best available therapy (BAT) in SM-AHN. Aims: This study (NCT04695431) compared OS between SM-AHN patients treated with avapritinib in the EXPLORER and PATHFINDER trials versus SM-AHN patients treated with BAT in standard clinical practice. Methods: A multi-center, global, observational, retrospective chart review study was conducted at 6 study sites (4 European, 2 US) to identify and collect data from AdvSM patients who received BAT. SM-AHN patients were identified using inclusion/exclusion criteria similar to the EXPLORER and PATHFINDER trials. Patients receiving BAT could contribute data on multiple lines of therapy (LOTs) to the analysis; these data were compared with patient-level data from the EXPLORER and PATHFINDER trials. OS was defined as the time from avapritinib or BAT initiation to death from any cause; patients were censored at date of last follow-up if alive. Kaplan-Meier analysis was used to assess OS. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in key variables between the treatment cohorts, including age, sex, region, anemia, thrombocytopenia, leukocyte count, skin involvement, number and type of prior treatments, performance status, serum tryptase level, and presence of SRSF2/ASXL1/RUNX1 mutations. An IPTW-weighted Cox proportional hazards model, adjusted for variables that remained unbalanced after weighting, was used to compare OS between treatment groups. Results: This analysis included 119 avapritinib patients and 83 BAT patients with SM-AHN (the latter contributed data on 121 LOTs). Median (range) age of the avapritinib and BAT cohorts was 70 (45−88) and 71 (38−88) years, and 61% vs. 76% of patients were male, respectively. Prior systemic therapy was received by 58% of avapritinib and 44% of BAT patients. In the avapritinib cohort, 76% of patients from both trials were dosed at ≤200mg and 24% of patients, all from EXPLORER, were dosed at ≥300mg. BAT patients were most frequently treated with tyrosine kinase inhibitors (73 out of 121 LOTs, 60%) or cytoreductive therapies (46 out of 121 LOTs, 38%). Mean durations of follow-up were 17.6 and 18.1 months, with 29 (24%) and 56 (68%) deaths in avapritinib and BAT cohorts, respectively. Median OS for avapritinib was 46.9 months (95% CI: 44.9, not estimable) and 18.0 months (95% CI: 13.0, 26.8) for BAT (Figure 1). IPTW-adjusted median OS was 46.9 months (95% CI: 21.4, 49.0) for avapritinib and 19.5 months (95% CI: 13.0, 32.2) for BAT. Weighted Cox analysis showed that OS was significantly improved for avapritinib versus BAT (hazard ratio [95% CI]: 0.42 [0.24, 0.74]; P<0.001), even with further adjustment for unbalanced variables. Image:Summary/Conclusion: The results of this analysis indicate that patients with SM-AHN treated with avapritinib in clinical trials had significantly longer OS compared to patients treated with BAT. With no RCTs, these data offer crucial insights into the survival benefit of SM-AHN patients treated with avapritinib compared to other treatments for AdvSM.